Compounds and methods for treating HIV infection

Abstract

Provided herein, inter alia, are methods and compounds for treating an HIV infection.

What is claimed is: 
     
       1. A compound having the formula: 
       
         
           
           
               
               
           
         
         wherein, 
         R 1  is substituted or unsubstituted cycloalkyl, substituted or unsubstituted piperazinyl, substituted or unsubstituted piperidinyl, substituted or unsubstituted pyrrolidinyl, substituted or unsubstituted azetidinyl, substituted or unsubstituted aziridinyl, substituted or unsubstituted 4,5,6,7-tetrahydrothie no[3,2-b]pyridine, substituted or unsubstituted 1,2,3,4-tetrahydroisoquinolinyl, or substituted or unsubstituted 1,4,6,7-tetrahydro-5λ 2 -pyrazolo[4,3-c]pyridinyl; 
         R 2  is hydrogen or —NR 2A R 2B ; 
         R 3  is hydrogen, halogen, —CX 3   3 , —CHX 3   2 , —CH 2 X 3 , —OCX 3   3 , —OCH 2 X 3 , —OCHX 3   2 , —CN, —SO n3 R 3D , SO v3 NR 3A R 3B , —NHC(O)NR 3A R 3B , —N(O) m3 ,—NR 3A R 3B , —C(O)R 3C , —C(O)—OR 3C , —C(O)NR 3A R 3B , —OR 3D , —NR 3A SO 2 R 3D , —NR 3A C(O)R 3C , —NR 3A C(O)OR 3C , —NR 3A OR 3C , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; 
         R 4  is independently hydrogen, halogen, —CX 4   3 , —CHX 4   2 , —CH 2 X 4 , —OCX 4   3 , —OCH 2 X 4 , —OCHX 4   2 , —CN, —SO n4 R 4D , —SO v4 NR 4A R 4B , —NHC(O)NR 4A R 4B , —N(O) m4 , —NR 4A R 4B , —C(O)R 4C , —C(O)—OR 4C , —C(O)NR 4A R 4B , —OR 4D , —NR 4A SO 2 R 4D , —NR 4A C(O)R 4C , —NR 4A C(O)OR 4C , —NR 4A OR 4C , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; 
         Each R 1A , R 1B , R 1C , R 1D , R 2A , R 2B , R 2C , R 2D , R 3A , R 3B , R 3C , R 3D , R  4A , R 4B , R 4C , and R 4D is independently hydrogen, —CX 3 , —CN, —NH 2 , —COOH, —CONH 2 , —CHX 2 , —CH 2 X, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; R 1A  and R 1B  substituents bonded to the same nitrogen atom may optionally be joined to form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl; R 2A  and R 2B  substituents bonded to the same nitrogen atom may optionally be joined to form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl; R 3A  and R 3B  substituents bonded to the same nitrogen atom may optionally be joined to form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl; R 4A  and R 4B  substituents bonded to the same nitrogen atom may optionally be joined to form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl; 
         each X, X 1 , X 2 , X 3 , and X 4 , is independently —F, —Cl, —Br, or —I; 
         n1, n3, and n4 are independently an integer from 0 to 4; and 
         m1, m3, m4, v1, v3, and v4 are independently an integer from 1 to 2. 
       
     
     
       2. The compound of  claim 1  having the formula: 
       
         
           
           
               
               
           
         
         wherein 
         R 3A  is hydrogen, —CX 3A   3 , —CHX 3A   2 , —CH 2 X 3A  , —C(O)NH 2 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; and 
         each X 3A  is independently —F, —Cl, —Br, or —I. 
       
     
     
       3. The compound of  claim 2  wherein R 3A  is hydrogen. 
     
     
       4. The compound of  claim 2  wherein R 2  is hydrogen. 
     
     
       5. The compound of  claim 2 , wherein R 1  is R 20 -substituted or unsubstituted piperazinyl, R 20 -substituted or unsubstituted piperidinyl, R 20 -substituted or unsubstituted pyrrolidinyl, R 20 -substituted or unsubstituted 4,5,6,7-tetrahydrothieno[3,2-b]pyridine, or R 20 -substituted or unsubstituted 1,2,3,4-tetrahydroisoquinolinyl, or R 20 -substituted or unsubstituted 1,4,6,7-tetrahydro-5λ 2 -pyrazolo[4,3-c]pyridinyl;
 R 20  is independently oxo, halogen, —CX 20   3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)OH, —NHC(O)OH, —NHOH, —OCX 20   3 , —OCHX 20   2 , substituted or unsubstituted C 1 -C 8  alkyl, substituted or unsubstituted 2 to 8 membered heteroalkyl, substituted or unsubstituted C 3 -C 8  cycloalkyl, substituted or unsubstituted 3 to 6 membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted 5 to 6 membered heteroaryl; and 
 X 20  is —F, —Cl, —Br, or —I. 
 
     
     
       6. The compound of  claim 2 , having the formula: 
       
         
           
           
               
               
           
         
       
     
     
       7. The compound of  claim 2 , having the formula: 
       
         
           
           
               
               
           
         
       
     
     
       8. The compound of  claim 5 , wherein R 20  is independently halogen, —CONH 2 , substituted or unsubstituted C 1 -C 8  alkyl, substituted or unsubstituted C 1 -C 8  alkoxy, substituted or unsubstituted C 3 -C 8  cycloalkoxy, substituted or unsubstituted 3 to 6 membered heterocycloalkoxy, substituted or unsubstituted phenoxy, substituted or unsubstituted phenyl, substituted or unsubstituted 5 to 6 membered heteroaryl, or substituted or unsubstituted 5 to 6 membered heteroaryloxy. 
     
     
       9. A method of inhibiting the level of Rev protein activity, inhibiting human immunodeficiency virus (HIV) virion formation in an HIV infected cell, inhibiting HIV viral shedding from an HIV infected cell, inhibiting HIV proliferation, treating an HIV infection, inhibiting the level of HIV Vpu activity in a cell, or modulating an HIV Vpu gene, said method comprising administering to a subject in need thereof an effective amount of a compound having the formula: 
       
         
           
           
               
               
           
         
         wherein, 
         R 1  is hydrogen, halogen, —CX 1    3 , —CHX 1   2 , —CH 2 X 1 , —OCX 1   3 , —OCH 2 X 1 , —OCHX 1   2 , —CN, —SO n1 R 1D , —SO v1 NR 1A R 1B , —NHC(O)NR 1A R 1B , —N(O) m1 , —NR 1A R 1B , —C(O)R 1C , —C(O)—OR 1C , —C(O)NR 1A R 1B , —OR 1D , —NR 1A SO 2 R 1D , —NR 1A C(O)R 1C , —NR 1A C(O)OR 1C , —NR 1A OR 1C , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; 
         R 2  is hydrogen, —NR 2A R 2B , —C(O)—R 2C , —C(O)—OR 2C , —C(O)NR 2A R 2B , —OR 2D , —NR 2A SO 2 R 2D , —NR 2A C(O)R 2C , —NR 2A C(O)OR 2C , —NR 2A OR 2C , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; 
         R 3  is hydrogen, halogen, —CX 3   3 , —CHX 3   2 , —CH 2 X 3 , —OCX 3   3 , —OCH 2 X 3 , —OCHX 3   2 , —CN, —SO n3 R 3D , —SO v3 NR 3A R 3B , —NHC(O)NR 3A R 3B , —N(O) m3 , —NR 3A R 3B , —C(O)R 3C , —C(O)—OR 3C , —C(O)NR 3A R 3B , —OR 3D , —NR 3A SO 2 R 3D , —NR 3A C(O)R 3C , —NR 3A C(O)OR 3C , —NR 3A OR 3C , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; 
         R 4 , R 4A1 , and R 4B1  are independently hydrogen, halogen, —CX 4   3 , —CHX 4   2 , —CH 2 X 4 , —OCX 4   3 , —OCH 2 X 4 , —OCHX 4   2 , —CN, —SO n4 R 4D , —SO v4 NR 4A R 4B , —NHC(O)NR 4A R 4B , —N(O) m4 , —NR 4A R 4B , —C(O)R 4C , —C(O)—OR 4C , —C(O)NR 4A R 4B , —OR 4D , —NR 4A SO 2 R 4D , —NR 4A C(O)R 4C , —NR 4A C(O)OR 4C , —NR 4A OR 4C , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; R 4  and R 4A1  may optionally be joined to form a substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; 
         Each R 1A , R 1B , R 1C , R 1D , R 2A , R 2B , R 2C , R 2D , R 3A , R 3B ,R 3C , R 3D , R 4A , R 4B , R 4C , and R 4D  is independently hydrogen, —CX 3 , —NH 2 , —CN, —COOH, —CONH 2 , —CHX 2 , —CH 2 X, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; R 1A  and R 1B  substituents bonded to the same nitrogen atom may optionally be joined to form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl; R 2 A and R 2 B substituents bonded to the same nitrogen atom may optionally be joined to form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl; R 3 A and R 3 B substituents bonded to the same nitrogen atom may optionally be joined to form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl; R 4 A and R 4 B substituents bonded to the same nitrogen atom may optionally be joined to form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl; 
         each X, X 1 , X 2 , X 3 , and X 4  is independently —F, —Cl, —Br, or —I; 
         n1, n3, and n4 are independently an integer from 0 to 4; and 
         m1, m3, m4, v1, v 3 , and v4 are independently an integer from 1 to 2; and 
         Y 1  is N and Y 2  is CR 4B1 . 
       
     
     
       10. The method of  claim 9 , wherein the compound has the formula: 
       
         
           
           
               
               
           
         
         wherein 
         R 3A  is hydrogen, —CX 3A   3 , —CHX 3A   2 , —CH 2 X 3A , —C(O)NH 2 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; and each X 3A  is independently —F, —Cl, —Br, or —I. 
       
     
     
       11. The method of  claim 9 , wherein the compound has the formula: 
       
         
           
           
               
               
           
         
       
     
     
       12. The method of  claim 9 , wherein the method is inhibiting the level of Rev protein activity, inhibiting HIV virion formation in an HIV infected cell, inhibiting HIV viral shedding from an HIV infected cell, inhibiting HIV proliferation, or treating an HIV infection. 
     
     
       13. The method of  claim 9 , wherein the method is inhibiting the level of HIV Vpu activity in a cell or modulating an HIV Vpu gene. 
     
     
       14. A compound having the following formula: 
       
         
           
           
               
               
           
         
       
     
     
       15. A compound of  claim 2 , having the formula: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
       16. The method of  claim 9 , wherein the method is treating an HIV infection. 
     
     
       17. The method of  claim 9  wherein R 3A  is hydrogen and R 2  is hydrogen. 
     
     
       18. A pharmaceutical composition comprising the compound of any one of  claims 1  to  8 ,  14 , or  15  and a pharmaceutically acceptable excipient. 
     
     
       19. The pharmaceutical composition of  claim 18 , further comprising an anti-viral agent. 
     
     
       20. The pharmaceutical composition of  claim 19 , wherein the anti-viral agent is an human immunodeficiency virus (HIV) reverse transcriptase inhibitor, human immunodeficiency virus (HIV) protease inhibitor, human immunodeficiency virus (HIV) integrase inhibitor, human immunodeficiency virus (HIV) fusion inhibitor, or human immunodeficiency virus (HIV) entry inhibitor.